Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo

Abstract

Data from many laboratory and clinical investigations indicate that CD34+ cells comprise approximately 1% of human bone marrow (BM) mononuclear cells, including the progenitor cells of all the lymphohematopoietic lineages and lymphohematopoietic stem cells (stem cells). Because stem cells are an important but rare cell type in the CD34+ cell population, investigators have subdivided the CD34+ cell population to further enrich stem cells. The CD34+/CD38-cell subset comprises less than 10% of human CD34+ adult BM cells (equivalent to < 0.1% of marrow mononuclear cells), lacks lineage (lin) antigens, contains cells with in vitro replating capacity, and is predicted to be highly enriched for stem cells. The present investigation tested whether the CD34+/CD38-subset of adult human marrow generates human hematopoiesis after transfer to preimmune fetal sheep. CD34+/ CD38- cells purified from marrow using immunomagnetic microspheres or fluorescence-activated cell sorting generated easily detectable, long- term, multilineage human hematopoiesis in the human-fetal sheep in vivo model. In contrast, transfer of CD34+/CD38+ cells to preimmune fetal sheep generated only short-term human hematopoiesis, possibly suggesting that the CD34+/CD38+ cell population contains relatively early multipotent hematopoletic progenitor cells, but not stem cells. This work extends the prior in vitro evidence that the earliest cells in fetal and adult human marrow lack CD38 expression. In summary, the CD34+/ CD38-cell population has a high capacity for long-term multilineage hematopoietic engraftment, suggesting the presence of stem cells in this minor adult human marrow cell subset.

Prognostic impact of the CD34+/CD38− cell burden in patients with acute myeloid leukemia receiving allogeneic stem cell transplantation

“…The phenotype of HSCs is not well defined, but HSCs have been suggested to be part of the primitive CD34+/CD38− cell population . A high amount of the CD34+/CD38− cells seem to rest in the G0 cell cycle phase, and are able to initiate retransplantable hematopoiesis in animal models …”

Sheep CD34+ Amniotic Fluid Cells Have Hematopoietic Potential and Engraft After Autologous In Utero Transplantation

“…This resulted in a multilineage hematopoietic chimerism that persisted for many years and ranged from 10% to 15% donor cell expression . The human‐to‐sheep model of IUSCT has proven to be an invaluable tool in the identification, characterization, and quantification of human HSC from several sources and this xenograft model of human hematopoiesis can serve as an accurate model to study in vivo mobilization of human HSCs .…”

Haematopoietic stem cells1

“…An essential feature of this model is that human HSCs primarily engraft host marrow and persist for long periods into post‐natal life44–46, showing multi‐lineage expression and biological responsiveness to human cytokines45. The multi‐lineage expression included T‐ and B‐lymphoid cells48. Furthermore, this model is relatively specific of the human HSC pool.…”